Driving Biomedical Projects Abstract The National Resource for Translational and Developmental Proteomics (NRTDP) will collaborate with geographically diverse investigators to complete eight Driving Biomedical Projects (DBPs) seeking advances that require top-down proteomics in four pillars of biomedical research. While these projects arise from disparate areas of science and medicine, each project cannot be performed optimally with the technology available at this point in time. These projects drive the Technology Research and Development (TR&D) projects of the NRTDP forward ? giving them a tangible and quantifiable goal with the overarching goal to impact and improve human health. Our TR&D projects focus on specific technologies throughout the progression of each DBP from accelerating top-down robustness to innovating novel targeted and discovery approaches from specific cell types. Integrating parts of each TR&D project, we have arranged our eight DBPs around four pillars (described in detail in the Overall section): Specific Aim 1 (Pillar 1): Cancer Proteomics. Top-down proteomics of p53, RAS, and H3.3K27M. Specific Aim 2 (Pillar 2): Immunoproteomics. Top-down analysis of multi-drug resistant ESKAPE pathogens and identification of transplant rejection markers using quantitative top-down proteomics. Specific Aim 3 (Pillar 3): Neuroproteomics. A specific focus on brain cancer and proteinopathies with roles in neurodegeneration and aging. Specific Aim 4 (Pillar 4): Cardiac Proteomics. Identifying the repertoire of ApoC-III proteoforms associated with coronary artery disease. It is through the integrated development of next generation proteomics technologies that we will be able to achieve success in Driving Biomedical Projects within these four pillars. As these projects progress throughout the lifetime of the grant, they will be reassessed and once technologies are matured, may be translated into Collaboration and Service projects, allowing new biomedical problems to drive the next generation of technology.